482 research outputs found
Circulating omentin concentration increases after weight loss
Omentin-1 is a novel adipokine expressed in visceral adipose tissue
and negatively associated with insulin resistance and obesity. We aimed to study
the effects of weight loss-induced improved insulin sensitivity on circulating
omentin concentrations. METHODS: Circulating omentin-1 (ELISA) concentration in
association with metabolic variables was measured in 35 obese subjects (18 men,
17 women) before and after hypocaloric weight loss. RESULTS: Baseline circulating
omentin-1 concentrations correlated negatively with BMI (r = -0.58, p < 0.001),
body weight (r = -0.35, p = 0.045), fat mass (r = -0.67, p < 0.001), circulating
leptin (r = -0.7, p < 0.001) and fasting insulin (r = -0.37, p = 0.03).
Circulating omentin-1 concentration increased significantly after weight loss
(from 44.9 +/- 9.02 to 53.41 +/- 8.8 ng/ml, p < 0.001). This increase in
circulating omentin after weight loss was associated with improved insulin
sensitivity (negatively associated with HOMA value and fasting insulin, r =
-0.42, p = 0.02 and r = -0.45, p = 0.01, respectively) and decreased BMI (r =
-0.54, p = 0.001). CONCLUSION: As previously described with adiponectin,
circulating omentin-1 concentrations increase after weight loss-induced
improvement of insulin sensitivity
Study of caveolin-1 gene expression in whole adipose tissue and its subfractions and during differentiation of human adipocytes
Caveolins are 21-24 kDa integral membrane proteins that serve as
scaffolds to recruit numerous signaling molecules. Specific subclasses of
caveolae carry out specific functions in cell metabolism. In particular,
triglycerides are synthesized at the site of fatty acid entry in one of these
caveolae classes. OBJECTIVE AND METHODS: We studied the expression of caveolin-1
(CAV-1) gene in association with metabolic variables in 90 visceral and 55
subcutaneous adipose tissue samples from subjects with a wide range of fat mass,
in the stromovascular fraction (SVC) and isolated adipocytes, and during
differentiation of human adipocytes. RESULTS: CAV-1 gene expression was
significantly decreased in visceral adipose tissue (v-CAV-1) of obese subjects.
v-CAV-1 was positively associated with several lipogenic genes such as acetyl-coA
carboxylase (ACACA, r = 0.34, p = 0.004) and spot-14 (r = 0.33, p = 0.004). In
non-obese subjects v-CAV-1 also correlated with fatty acid synthase (FAS, r =
0.60, p < 0.0001). Subcutaneous (sc) adipose tissue (sc-CAV-1) gene expression
was not associated with these lipogenic factors when obese and non-obese subjects
were studied together. In obese subjects, however, sc-CAV-1 was associated with
fatty acid synthase (FAS, r = 0.36, p = 0.02), sterol regulatory element binding
protein-1c (SREBP-1c (r = 0.58, p < 0.0001), ACACA (r = 0.33, p = 0.03), spot-14
(r = 0.36, p = 0.02), PPAR-gamma co-activator-1 (PGC-1, r = 0.88, n = 19). In
these obese subjects, sc-CAV-1 was also associated with fasting triglycerides (r
= -0.50, p < 0.0001).CAV-1 expression in mature adipocytes was significantly
higher than in stromal vascular cells. CAV-1 gene expression in adipocytes from
subcutaneous adipose tissue (but not in adipocytes from visceral adipose tissue)
was significatively associated with fasting triglycerides. CAV-1 gene expression
did not change significantly during differentiation of human preadipocytes from
lean or obese subjects despite significant increase of FAS gene expression.
CONCLUSION: Decreased CAV-1 gene expression was simultaneously linked to
increased triglycerides and decreased lipogenic gene expression among obese
subjects, paralleling the observations of hypertriglyceridemia in CAV-1 knockout
mice. However, the regulation of CAV-1 gene expression seems independent of the
adipogenic program
Histological and ultrastructural comparison of cauterization and thrombosis stroke models in immune-deficient mice
Background: Stroke models are essential tools in experimental stroke. Although several models of stroke have
been developed in a variety of animals, with the development of transgenic mice there is the need to develop a
reliable and reproducible stroke model in mice, which mimics as close as possible human stroke.
Methods: BALB/Ca-RAG2-/-gc-/- mice were subjected to cauterization or thrombosis stroke model and sacrificed at
different time points (48hr, 1wk, 2wk and 4wk) after stroke. Mice received BrdU to estimate activation of cell
proliferation in the SVZ. Brains were processed for immunohistochemical and EM.
Results: In both stroke models, after inflammation the same glial scar formation process and damage evolution
takes place. After stroke, necrotic tissue is progressively removed, and healthy tissue is preserved from injury
through the glial scar formation. Cauterization stroke model produced unspecific damage, was less efficient and
the infarct was less homogeneous compared to thrombosis infarct. Finally, thrombosis stroke model produces
activation of SVZ proliferation.
Conclusions: Our results provide an exhaustive analysis of the histopathological changes (inflammation, necrosis,
tissue remodeling, scarring...) that occur after stroke in the ischemic boundary zone, which are of key importance
for the final stroke outcome. This analysis would allow evaluating how different therapies would affect wound and
regeneration. Moreover, this stroke model in RAG 2-/- gC -/- allows cell transplant from different species, even
human, to be analyzed
Design and evaluation of a treatment programme for Spanish adolescents with overweight and obesity. The EVASYON Study
Background
The prevalence of overweight and obesity (OW/OB) among adolescents worldwide has increased since the 60 s. Spain has reached one of the highest OW/OB prevalence rates among adolescents from European countries. The aim of this methodological paper is to describe the design and evaluation in the EVASYON study (Development, implementation and evaluation of the efficacy of a therapeutic programme for adolescents with OW/OB: integral education on nutrition and physical activity).
Methods/Design
The EVASYON was planned by a multidisciplinary team to treat OW/OB in Spanish adolescents. The EVASYON is a multi-centre study conducted in 5 hospitals in 5 Spanish cities (Granada, Madrid, Pamplona, Santander and Zaragoza) and two hundred and four OW/OB Spanish adolescents were recruited for this intervention. The treatment was implemented for approximately one-year follow-up. The adolescents were treated in groups of a maximum of 10 subjects; each group had 20 visits during the treatment period in two phases: intensive during the first 2 months (1st to 9th visits), and extensive during the last 11 months (10th to 20th visits). In order to assess the efficacy of the treatment, 8 dimensions were measured: diet; physical activity and fitness; eating behaviour; body composition; haematological profile; metabolic profile; minerals and vitamins; immuno-inflammatory markers. Moreover, genetic polymorphisms were also determined.
Discussion
The treatment programme developed in the EVASYON study was designed as a national pilot study to be implemented as an effective treatment for adolescents with OW/OB into the Spanish Health Care Service
Therapeutic effects of hMAPC and hMSC transplantation after stroke in mice
Stroke represents an attractive target for stem cell therapy. Although different types of cells have been employed in animal models, a direct comparison between cell sources has not been performed. The aim of our study was to assess the effect of human multipotent adult progenitor cells (hMAPCs) and human mesenchymal stem cells (hMSCs) on endogenous neurogenesis, angiogenesis and inflammation following stroke. BALB/Ca-RAG 2(-/-) ÎłC(-/-) mice subjected to FeCl(3) thrombosis mediated stroke were intracranially injected with 2 Ă 10(5) hMAPCs or hMSCs 2 days after stroke and followed for up to 28 days. We could not detect long-term engraftment of either cell population. However, in comparison with PBS-treated animals, hMSC and hMAPC grafted animals demonstrated significantly decreased loss of brain tissue. This was associated with increased angiogenesis, diminished inflammation and a glial-scar inhibitory effect. Moreover, enhanced proliferation of cells in the subventricular zone (SVZ) and survival of newly generated neuroblasts was observed. Interestingly, these neuroprotective effects were more pronounced in the group of animals treated with hMAPCs in comparison with hMSCs. Our results establish cell therapy with hMAPCs and hMSCs as a promising strategy for the treatment of strok
HTLV-1 infection in solid organ transplant donors and recipients in Spain
HTLV-1 infection is a neglected disease, despite infecting 10-15 million people worldwide and severe illnesses develop in 10% of carriers lifelong. Acknowledging a greater risk for developing HTLV-1 associated illnesses due to immunosuppression, screening is being widely considered in the transplantation setting. Herein, we report the experience with universal HTLV testing of donors and recipients of solid organ transplants in a survey conducted in Spain. All hospitals belonging to the Spanish HTLV network were invited to participate in the study. Briefly, HTLV antibody screening was performed retrospectively in all specimens collected from solid organ donors and recipients attended since the year 2008. A total of 5751 individuals were tested for HTLV antibodies at 8 sites. Donors represented 2312 (42.2%), of whom 17 (0.3%) were living kidney donors. The remaining 3439 (59.8%) were recipients. Spaniards represented nearly 80%. Overall, 9 individuals (0.16%) were initially reactive for HTLV antibodies. Six were donors and 3 were recipients. Using confirmatory tests, HTLV-1 could be confirmed in only two donors, one Spaniard and another from Colombia. Both kidneys of the Spaniard were inadvertently transplanted. Subacute myelopathy developed within 1 year in one recipient. The second recipient seroconverted for HTLV-1 but the kidney had to be removed soon due to rejection. Immunosuppression was stopped and 3 years later the patient remains in dialysis but otherwise asymptomatic. The rate of HTLV-1 is low but not negligible in donors/recipients of solid organ transplants in Spain. Universal HTLV screening should be recommended in all donor and recipients of solid organ transplantation in Spain. Evidence is overwhelming for very high virus transmission and increased risk along with the rapid development of subacute myelopathy
Isotemporal substitution of inactive time with physical activity and time in bed: cross-sectional associations with cardiometabolic health in the PREDIMEDPlus study
Background: This study explored the association between inactive time and measures of adiposity, clinical parameters, obesity, type 2 diabetes and metabolic syndrome components. It further examined the impact of reallocating inactive time to time in bed, light physical activity (LPA) or moderate-to-vigorous physical activity (MVPA) on cardio-metabolic risk factors, including measures of adiposity and body composition, biochemical parameters and blood pressure in older adults.
Methods: This is a cross-sectional analysis of baseline data from 2189 Caucasian men and women (age 55-75 years, BMI 27-40 Kg/m2) from the PREDIMED-Plus study (http://www.predimedplus.com/). All participants had â„3 components of the metabolic syndrome. Inactive time, physical activity and time in bed were objectively determined using triaxial accelerometers GENEActiv during 7 days (ActivInsights Ltd., Kimbolton, United Kingdom). Multiple adjusted linear and logistic regression models were used. Isotemporal substitution regression modelling was performed to assess the relationship of replacing the amount of time spent in one activity for another, on each outcome, including measures of adiposity and body composition, biochemical parameters and blood pressure in older adults.
Results: Inactive time was associated with indicators of obesity and the metabolic syndrome. Reallocating 30 min per day of inactive time to 30 min per day of time in bed was associated with lower BMI, waist circumference and glycated hemoglobin (HbA1c) (all p-values < 0.05). Reallocating 30 min per day of inactive time with 30 min per day of LPA or MVPA was associated with lower BMI, waist circumference, total fat, visceral adipose tissue, HbA1c, glucose, triglycerides, and higher body muscle mass and HDL cholesterol (all p-values < 0.05).
Conclusions: Inactive time was associated with a poor cardio-metabolic profile. Isotemporal substitution of inactive time with MVPA and LPA or time in bed could have beneficial impact on cardio-metabolic health
Dietary diversity and nutritional adequacy among an older Spanish population with Metabolic Syndrome in the PREDIMED-Plus study: a cross-sectional analysis
Dietary guidelines emphasize the importance of a varied diet to provide an adequate nutrient intake. However, an older age is often associated with consumption of monotonous diets that can be nutritionally inadequate, increasing the risk for the development or progression of diet-related chronic diseases, such as metabolic syndrome (MetS). To assess the association between dietary diversity (DD) and nutrient intake adequacy and to identify demographic variables associated with DD, we cross-sectionally analyzed baseline data from the PREDIMED-Plus trial: 6587 Spanish adults aged 55â75 years, with overweight/obesity who also had MetS. An energy-adjusted dietary diversity score (DDS) was calculated using a 143-item validated semi-quantitative food frequency questionnaire (FFQ). Nutrient inadequacy was defined as an intake below 2/3 of the dietary reference intake (DRI) forat least four of 17 nutrients proposed by the Institute of Medicine (IOM). Logistic regression models were used to evaluate the association between DDS and the risk of nutritionally inadequate intakes. In the higher DDS quartile there were more women and less current smokers. Compared with subjects in the highest DDS quartile, those in the lowest DDS quartile had a higher risk of inadequate nutrient intake: odds ratio (OR) = 28.56 (95% confidence interval (CI) 20.80â39.21). When we estimated food varietyfor each of the food groups, participants in the lowest quartile had a higher risk of inadequate nutrient intake for the groups of vegetables, OR = 14.03 (95% CI 10.55â18.65), fruits OR = 11.62 (95% CI 6.81â19.81), dairy products OR = 6.54 (95% CI 4.64â9.22) and protein foods OR = 6.60 (95% CI 1.96â22.24). As DDS decreased, the risk of inadequate nutrients intake rose. Given the impact of nutrient intake adequacy on the prevention of non-communicable diseases, health policies should focus on the promotion of a healthy varied diet, specifically promoting the intake of vegetables and fruit among population groups with lower DDS such as men, smokers or widow(er)s. View Full-Tex
Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants
Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Peer reviewe
Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry
Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase
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